帕金森病鼻内治疗的研究进展

Neuroprotection Pub Date : 2024-04-21 DOI:10.1002/nep3.42
Puyuan Wen, Chao Ren
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摘要

帕金森病(PD)是全球发病率第二高的神经退行性疾病,严重影响患者的生活质量。由于首过代谢、血脑屏障(BBB)和血-脑脊液屏障的影响,全身给药到大脑的效率很低。随着病情的发展,这种低效率导致必须增加剂量,从而产生严重的副作用,影响药物的疗效。鼻入脑(N2B)给药可绕过 BBB,将小分子和大分子蛋白质物质输送到中枢神经系统。与全身给药相比,这种方法提高了脑生物利用度,减少了酶降解,并将全身不良反应降至最低。然而,N2B 给药系统也面临着一些严峻的挑战,包括粘膜清除、酶降解和药物通过外流机制转运。本文从临床前研究和临床研究两方面全面概述了目前鼻内治疗帕金森病的研究进展,并讨论了其给药系统的生理方面和局限性。
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Research progress on intranasal treatment for Parkinson's disease
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder globally, significantly affecting the quality of life of affected individuals. Systemic drug delivery to the brain is inefficient because of first‐pass metabolism, the blood‐brain barrier (BBB), and the blood‐cerebrospinal fluid barrier. This inefficiency necessitates increased dosage as the disease progresses, leading to severe side effects that compromise the efficacy of the medication. Nose‐to‐brain (N2B) administration bypasses the BBB, allowing delivery of both small molecules and large protein substances to the central nervous system. Compared with systemic administration, this method enhances brain bioavailability, reduces enzymatic degradation, and minimizes systemic adverse reactions. However, the N2B delivery system is associated with several critical challenges, including mucociliary clearance, enzymatic degradation, and drug translocation via efflux mechanisms. This paper provides a comprehensive overview of the current research progress in intranasal treatment of PD, considering both preclinical and clinical studies, and discusses the physiological aspects and limitations of its delivery system.
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